A5029784389- Adipose Tissue and Metabolism
- Bee Products Chemical Analysis
- Diet, Metabolism, and Disease
- Adipokines, Inflammation, and Metabolic Diseases
- Insect and Pesticide Research
- Neuropeptides and Animal Physiology
- Pancreatic function and diabetes
- Alcohol Consumption and Health Effects
- Enzyme Structure and Function
- Plant and animal studies
- Cardiovascular Disease and Adiposity
- Liver Disease Diagnosis and Treatment
- Enzyme Catalysis and Immobilization
- Amino Acid Enzymes and Metabolism
- Essential Oils and Antimicrobial Activity
- Endoplasmic Reticulum Stress and Disease
- Advanced Glycation End Products research
- Metabolism and Genetic Disorders
- Fibroblast Growth Factor Research
- Cancer, Hypoxia, and Metabolism
- Aldose Reductase and Taurine
- Regulation of Appetite and Obesity
- Biomedical Research and Pathophysiology
- Chronic Kidney Disease and Diabetes
- Glycosylation and Glycoproteins Research
Maurice Wilkins Centre
2016-2025
University of Auckland
2016-2025
Karolinska Institutet
1991-1993
Massey University
1985-1990
Adipose tissue macrophage (ATM) inflammation is involved with meta-inflammation and pathology of metabolic complications. Here we report that in adipocytes, elevated lactate production, previously regarded as the waste product glycolysis, serves a danger signal to promote ATM polarization an inflammatory state context obesity. Adipocyte-selective deletion dehydrogenase A (Ldha), enzyme converting pyruvate lactate, protects mice from obesity-associated glucose intolerance insulin resistance,...
Abstract Aging in mammals is accompanied by an imbalance of intestinal homeostasis and accumulation mitochondrial DNA (mtDNA) mutations. However, little known about how accumulated mtDNA mutations modulate homeostasis. We observe the small intestine aged male mice, suggesting association with physiological aging. Using polymerase gamma (POLG) mutator mice wild-type we generate progressive mutation burdens. Investigation utilizing organoid technology vivo stem cell labeling reveals decreased...
Adipose browning has demonstrated therapeutic potentials in several diseases. Here, by conducting transcriptomic profiling at the single-cell and single-nucleus resolution, we reconstituted cellular atlas mouse inguinal subcutaneous white adipose tissue (iWAT) thermoneutrality or chronic cold condition. All major nonimmune cells within iWAT, including stem progenitor (ASPCs), mature adipocytes, endothelial cells, Schwann smooth muscle were recovered, allowing us to uncover an overall...
Altered metabolism of the inositol sugars myo -inositol (MI) and d - chiro is implicated in diabetic complications. In animals, catabolism MI depends on enzyme oxygenase (MIOX), which catalyzes first committed step glucuronate–xylulose pathway, found almost exclusively kidneys. The crystal structure MIOX, complex with MI, has been determined by multiwavelength anomalous diffraction methods refined at 2.0-Å resolution ( R = 0.206, free 0.253). reveals a monomeric, single-domain protein mostly...
Alpha-calcitonin gene-related peptide (alphaCGRP) is a neuropeptide that expressed in motor and sensory neurons. It powerful vasodilator has been implicated diverse metabolic roles. However, its precise physiological function remains unclear. In this study, we investigated the role of alphaCGRP lipid metabolism by chronically challenging alphaCGRP-specific knockout (alphaCGRP(-/-)) control mice with high-fat diet regimens. At start both animal groups displayed similar body weights, serum...
Hepatosteatosis, defined as excessive intrahepatic lipid accumulation, represents the first step of nonalcoholic fatty liver disease (NAFLD). When combined with additional cellular stress, this benign status progresses to local and systemic pathological conditions such steatohepatitis insulin resistance. However, molecular events directly caused by hepatic buildup, in terms its impact on biology peripheral organs, remain unclear. Carnitine palmitoyltransferase 1A (CPT1A) is rate-limiting...
Rationale: Brown and beige adipocytes are specialized fat cells that dissipate energy in the form of heat, hold therapeutic potential for obesity metabolic diseases. Although classical viewpoint brown solely via uncoupling protein 1 (UCP1), emerging evidence suggests importance non-canonical UCP1-independent expenditure regulating expenditure, especially human adipocytes. Leucine zipper-, EF-hand-containing transmembrane domain containing (LETMD1) was recently identified as a key maintaining...
We report the design, optimization, and biological evaluation of nuclear receptor RORγ inverse agonists as therapeutic agents for prostate cancer treatment. The most potent compound 27 (designated XY101) exhibited cellular activity with an IC50 value 30 nM in a cell-based reporter gene assay good selectivity against other subtypes. cocrystal structure complex ligand binding domain provided solid structural basis its antagonistic mechanism. potently inhibited cell growth, colony formation,...
There is a significant correlation between the occurrence of pancreatic islet amyloid and β-cell failure in advanced type II diabetes mellitus. Islet composed primarily fibrillar form hormone, amylin. Using thioflavin-T fluorescence binding radioprecipitation assays, we investigated whether or not series small tricyclic compounds, tetracycline Congo Red could interfere with conversion synthetic human amylin into its insoluble form. Of compounds investigated, incubation 20-fold molar excess...
OBJECTIVE Aggregation of human amylin/islet amyloid polypeptide (hA/hIAPP) into small soluble β-sheet–containing oligomers is linked to islet β-cell degeneration and the pathogenesis type 2 diabetes. Here, we used tetracycline, which modifies hA/hIAPP oligomerization, probe mechanisms whereby causes diabetes in hemizygous hA/hIAPP-transgenic mice. RESEARCH DESIGN AND METHODS We chronically treated transgenic mice with oral tetracycline determine its effects on rates initiation, progression,...
Misfolding of the islet β-cell peptide hA (human amylin) into β-sheet-containing oligomers is linked to apoptosis and pathogenesis T2DM (Type 2 diabetes mellitus). In present study, we have investigated possible effects on misfolding chaperones HSP (heat-shock protein) 70, GRP78/BiP (glucose-regulated protein 78 kDa/immunoglobulin heavy-chain-binding HSP40/DnaJ. We demonstrate that underwent spontaneous time-dependent β-sheet formation aggregation by thioflavin-T fluorescence in solution,...
Renal depletion of myo-inositol (MI) is associated with the pathogenesis diabetic nephropathy in animal models, but underlying mechanisms involved are unclear. We hypothesized that MI was due to changes inositol metabolism and therefore examined expression genes regulating de novo biosynthesis, reabsorption, catabolism MI. also extended analyses from diabetes mellitus models dietary-induced obesity hypertension. found renal pervasive across these three distinct disease states relative order:...
Abstract We report a new method herein coined SP‐CLipPA (solid‐phase cysteine lipidation of peptide or amino acid) for the synthesis mono‐S‐lipidated peptides. This technique utilizes thiol–ene chemistry conjugation vinyl ester to free thiol semiprotected, resin‐bound peptide. Advantages include: ease handling, conversions up 91 %, by‐product removal by simple filtration, and single purification step. Additionally, desired lipidated products show high chromatographic separation from...
Abstract PRDM16 (PR domain containing protein 16) serves as a dominant activator of brown and beige adipocyte. However, mechanisms underlying the regulation expression are incompletely understood. A Prdm16 luciferase knockin reporter mouse model is generated, enabling high throughput monitoring transcription. Single clonal analysis reveals heterogeneity in inguinal white adipose tissue (iWAT) cells. Amongst all transcription factors, androgen receptor ( Ar ) shows strongest negative...
The T-box gene Tbx15 is abundantly expressed in adipose tissues, especially subcutaneous and brown fat. Although its expression correlated with obesity, precise biological role tissue poorly understood vivo. Here we investigated the function of thermogenesis white browning In present study, generated adipose-specific knockout (AKO) mice by crossing floxed adiponectin-Cre to delineate tissues. We systematically influence on mice, as well possible underlying molecular mechanism. Upon cold...
Ma̅nuka honey, made from the nectar of Leptospermum scoparium, has garnered scientific and economical interest due to its nonperoxide antibacterial activity. Biomarkers for genuine ma̅nuka honey are increasingly in demand presence counterfeit honey. This work reports identification a compound previously unreported by HPLC, determination structure as 3,6,7-trimethyllumazine using NMR, MS, IR, UV/vis spectroscopy. assignment was confirmed total synthesis. The natural product, renamed...